scholarly journals Influenza A Virus Induces Interleukin-27 through Cyclooxygenase-2 and Protein Kinase A Signaling

2012 ◽  
Vol 287 (15) ◽  
pp. 11899-11910 ◽  
Author(s):  
Li Liu ◽  
Zhongying Cao ◽  
Jing Chen ◽  
Rui Li ◽  
Yanhua Cao ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Influenza A Virus ◽  
Influenza A ◽  
Mononuclear Cells ◽  
Cyclooxygenase 2 ◽  
Lung Epithelial Cells ◽  
Prostaglandin E ◽  
Immune Factor ◽  
Kinase A

We previously reported that IL-27, which belongs to the IL-12 family of cytokines, is elevated in the serum of patients infected with influenza A virus (IAV). Here, we show that the expression of IL-27 was significantly up-regulated in A549 human lung epithelial cells and human peripheral blood mononuclear cells infected with IAV. Additionally, IAV triggered IL-27 expression through protein kinase A and cAMP-response element-binding protein signaling, which was mediated by cyclooxygenase-2-derived prostaglandin E2. IL-27 inhibited IAV replication by STAT1/2/3 phosphorylation and activated antiviral factor protein kinase R phosphorylation. Clinical analysis showed that IL-27 levels were significantly elevated in a cohort of patients infected with IAV compared with healthy individuals and that circulating IL-27 levels were tightly and positively correlated with prostaglandin E2 levels. These results indicate that IL-27 expression is one host immune factor produced in response to IAV infection and that elevated IL-27 levels inhibit viral replication.

scholarly journals Regulation of transforming growth factor β-induced responses by protein kinase A in pancreatic acinar cells

2008 ◽  
Vol 295 (1) ◽  
pp. G170-G178 ◽  
Author(s):  
Huibin Yang ◽  
Cheong J. Lee ◽  
Lizhi Zhang ◽  
Maria Dolors Sans ◽  
Diane M. Simeone
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Transforming Growth Factor ◽  
Acinar Cells ◽  
Lung Epithelial Cells ◽  
Pancreatic Acinar Cells ◽  
Intracellular Camp ◽  
Physical Interaction ◽  
Pancreatic Acini ◽  
Kinase A

TGF-β is an important regulator of growth and differentiation in the pancreas and has been implicated in pancreatic tumorigenesis. We have recently demonstrated that TGF-β can activate protein kinase A (PKA) in mink lung epithelial cells (Zhang L, Duan C, Binkley C, Li G, Uhler M, Logsdon C, Simeone D. Mol Cell Biol 24: 2169–2180, 2004). In this study, we sought to determine whether TGF-β activates PKA in pancreatic acinar cells, the mechanism by which PKA is activated, and PKA's role in TGF-β-mediated growth regulatory responses. TGF-β rapidly activated PKA in pancreatic acini while having no effect on intracellular cAMP levels. Coimmunoprecipitation experiments demonstrated a physical interaction between a Smad3/Smad4 complex and the regulatory subunits of PKA. TGF-β also induced activation of the PKA-dependent transcription factor CREB. Both the specific PKA inhibitor H89 and PKI peptide significantly blocked TGF-β's ability to activate PKA and CREB. TGF-β-mediated growth inhibition and TGF-β-induced p21 and SnoN expression in pancreatic acinar cells were blocked by H89 and PKI peptide. This study demonstrates that this novel cross talk between TGF-β and PKA signaling pathways may play an important role in regulating TGF-β signaling in the pancreas.

scholarly journals Microsomal prostaglandin E synthase-1 regulates human glioma cell growth via prostaglandin E2–dependent activation of type II protein kinase A

2006 ◽  
Vol 5 (7) ◽  
pp. 1817-1826 ◽  
Author(s):  
Troy Payner ◽  
H. Anne Leaver ◽  
Brian Knapp ◽  
Ian R. Whittle ◽  
Ovidiu C. Trifan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Growth ◽  
Prostaglandin E2 ◽  
Protein Kinase A ◽  
Glioma Cell ◽  
Prostaglandin E ◽  
Type Ii ◽  
Human Glioma ◽  
Prostaglandin E Synthase ◽  
Kinase A

scholarly journals Prostaglandin E 2 ‐Stimulated Cl − Secretion in Airway Epithelium Involves Protein Kinase A and Calcium Crosstalk

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Shayda Abazari ◽  
Gopika Hari ◽  
Elizabeth Crowther ◽  
Franny Kiles ◽  
Annie Trumbull ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Airway Epithelium ◽  
Prostaglandin E ◽  
Cl Secretion ◽  
Kinase A

scholarly journals Peptidoglycan-Induced IL-6 Production in RAW 264.7 Macrophages Is Mediated by Cyclooxygenase-2, PGE2/PGE4 Receptors, Protein Kinase A, IκB Kinase, and NF-κB

2006 ◽  
Vol 177 (1) ◽  
pp. 681-693 ◽  
Author(s):  
Bing-Chang Chen ◽  
Chiao-Chun Liao ◽  
Ming-Jen Hsu ◽  
Yi-Ting Liao ◽  
Chia-Chin Lin ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Cyclooxygenase 2 ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Iκb Kinase ◽  
Kinase A

scholarly journals Downregulation of CIITA Function by Protein Kinase A (PKA)-Mediated Phosphorylation: Mechanism of Prostaglandin E, Cyclic AMP, and PKA Inhibition of Class II Major Histocompatibility Complex Expression in Monocytic Lines

2001 ◽  
Vol 21 (14) ◽  
pp. 4626-4635 ◽  
Author(s):  
Guoxuan Li ◽  
Jonathan A. Harton ◽  
Xinsheng Zhu ◽  
Jenny P.-Y. Ting
Keyword(s):  
Major Histocompatibility Complex ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Class Ii ◽  
Prostaglandin E ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Class Ii Mhc ◽  
Kinase A

ABSTRACT Prostaglandins, pleiotropic immune modulators that induce protein kinase A (PKA), inhibit gamma interferon induction of class II major histocompatibility complex (MHC) genes. We show that phosphorylation of CIITA by PKA accounts for this inhibition. Treatment with prostaglandin E or 8-bromo-cyclic AMP or transfection with PKA inhibits the activity of CIITA in both mouse and human monocytic cell lines. This inhibition is independent of other transcription factors for the class II MHC promoter. These same treatments also greatly reduced the induction of class II MHC mRNA by CIITA. PKA phosphorylation sites were identified using site-directed mutagenesis and phosphoamino acid analysis. Phosphorylation at CIITA serines 834 and 1050 accounts for the inhibitory effects of PKA on CIITA-driven class II MHC transcription. This is the first demonstration that the posttranslational modification of CIITA mediates inhibition of class II MHC transcription.

scholarly journals Novel role for prostaglandin E2 in fish hepatocytes: regulation of glucose metabolism

2002 ◽  
Vol 174 (1) ◽  
pp. 137-146 ◽  
Author(s):  
ER Busby ◽  
GA Cooper ◽  
TP Mommsen
Keyword(s):  
Protein Kinase ◽  
Glucose Metabolism ◽  
Protein Kinase A ◽  
Adenylyl Cyclase ◽  
Glycogen Phosphorylase ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Fish Liver ◽  
Prostaglandin Receptors ◽  
Kinase A

Prostaglandin E(2) (PGE(2)) potently activated glycogenolysis and gluconeogenesis in isolated rockfish (Sebastes caurinus) hepatocytes. The average degree of activation for glycogenolysis was 6.4+/-0.67-fold (mean+/-S.E.M.; n=37), and could be as much as 19-fold. Analysis of dose-concentration relationships between glycogenolytic actions and PGE(2) concentrations yielded an EC(50) around 120 nM in hepatocyte suspensions and 2 nM for hepatocytes immobilized on perifusion columns. For the activation of gluconeogenesis (1.74+/-0.14-fold; n=10), the EC(50) for suspensions was 60 nM. Intracellular targets for PGE(2) actions are adenylyl cyclase, protein kinase A and glycogen phosphorylase. Concentrations of cAMP increased with increasing concentrations of PGE(2), and peaked within 2 min of hormone application. In the presence of the phosphodiesterase inhibitor, isobutyl-3-methylxanthine, peak height was increased and peak duration extended. The protein kinase A inhibitor, Rp-cAMPS, counteracted the activation of glycogenolysis by PGE(2), implying that the adenylyl cyclase/protein kinase A pathway is the most important, if not exclusive, route of message transduction. PGE(2) activated plasma membrane adenylyl cyclase and hepatocyte glycogen phosphorylase in a dose-dependent manner. The effects were specific for PGE(2); smaller degrees of activation of glycogenolysis were noted for PGE(1), 11-deoxy PGE(1), 19-R-hydroxy-PGE(2), and prostaglandins of the A, B and Falpha-series. The selective EP(2)-receptor agonist, butaprost, was as effective as PGE(2), suggesting that rockfish liver contains prostaglandin receptors pharmacologically related to the EP(2) receptors of non-hepatic tissues of mammals. Rockfish hepatocytes quickly degraded added PGE(2) (t((1/2))=17-26 min). A similar ability to degrade PGE(2) has been noted in catfish (Ameiurus nebulosus) hepatocytes, but no glycogenolytic or gluconeogenic actions of the hormone are noted for this species. We conclude that PGE(2) is an important metabolic hormone in fish liver, with cAMP-mediated actions on glycogen and glucose metabolism, and probably other pathways regulated by cAMP and protein kinase A. The constant presence of EP(2)-like receptors is a unique feature of the fish liver, with interesting implications for function and evolution of prostaglandin receptors in vertebrates.

Asbestos-mediated CREB phosphorylation is regulated by protein kinase A and extracellular signal-regulated kinases 1/2

2007 ◽  
Vol 292 (6) ◽  
pp. L1361-L1369 ◽  
Author(s):  
Christy A. Barlow ◽  
Trisha F. Barrett ◽  
Arti Shukla ◽  
Brooke T. Mossman ◽  
Karen M. Lounsbury
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Protein Kinase A ◽  
Asbestos Exposure ◽  
Lung Epithelial Cells ◽  
Creb Phosphorylation ◽  
Extracellular Signal ◽  
Map Kinase Phosphatase ◽  
Lung Epithelial ◽  
Kinase A

Asbestos is a ubiquitous, naturally occurring fiber that has been linked to the development of malignant and fibrotic lung diseases. Asbestos exposure leads to apoptosis, followed by compensatory proliferation, yet many of the signaling cascades coupled to these outcomes are unclear. Because CREs (Ca2+/cAMP-response elements) are found in the promoters of many genes important for regulation of proliferation and apoptosis, CREB (CRE binding protein) is likely to play an important role in the development of asbestos-mediated lung injury. To explore this possibility, we tested the hypotheses that asbestos exposure leads to CREB phosphorylation in lung epithelial cells and that protein kinase A (PKA) and extracellular signal-regulated kinases 1/2 (ERK1/2) are central regulators of the CREB pathway. Persistent CREB phosphorylation was observed in lung sections from mice following inhalation of crocidolite asbestos. Exposure of C10 lung epithelial cells to crocidolite asbestos led to rapid CREB phosphorylation and apoptosis that was decreased by the inhibition of PKA or ERK1/2 using the specific inhibitors H89 and U0126, respectively. Furthermore, crocidolite asbestos selectively induced a sustained increase in MAP kinase phosphatase-1 mRNA and protein. Silencing CREB protein dramatically reduced asbestos-mediated ERK1/2 phosphorylation, yet significantly increased the number of cells undergoing asbestos-induced apoptosis. These data reveal a novel and selective role for CREB in asbestos-mediated signaling through pathways regulated by PKA and ERK1/2, further providing evidence that CREB is an important regulator of apoptosis in asbestos-induced responses of lung epithelial cells.

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